HKPocket: human kinase pocket database for drug design

Area of Science:

• Biochemistry
• Pharmacology
• Structural Biology

Background:

• Kinase pocket structural information is vital for developing targeted cancer therapies and other drugs.
• Existing databases lack direct applicability for kinase drug discovery studies.
• A comprehensive human kinase protein pocket database is essential.

Purpose of the Study:

• To develop a comprehensive database of human kinase protein pockets.
• To facilitate drug discovery and development by providing detailed pocket information.

Main Methods:

• Development of the Human Kinase Pocket (HKPocket) database.
• Inclusion of sequence, structure, hydrophilic-hydrophobic, interaction, and druggability data for 1717 pockets from 255 kinases.
• Clustering of pockets based on structural and positional features.

Main Results:

• The HKPocket database contains comprehensive data for 1717 kinase pockets.
• Pockets were categorized into 91 clusters, aiding in preliminary drug screening.
• Analysis of sequence conservation, interactions, and hydrophobicity supports drug selection and optimization.

Conclusions:

• The HKPocket database is a valuable tool for kinase drug screening and optimization.
• Targeting non-catalytic pockets may reduce drug side effects.
• The HKPocket database is publicly accessible online.